Comparison of prophylactic antibiotics in colorectal surgery

AORN Journal,  April, 2007  by George Allen

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The New England Journal of Medicine December 2006

Cefotetan and cefoxitin are the agents currently recommended for antibiotic prophylaxis in patients undergoing colorectal surgery; however, these two medications may not be available in the future because the manufacturers are planning to discontinue their production. Consequently, other options for antibiotic prophylaxis for colorectal surgery must be considered.

Ertapenem is a carbapenem antibiotic used in the treatment of complicated intra-abdominal infections, and it has several characteristics that make its use attractive as a potential antibiotic prophylactic agent for colorectal procedures. It can be rapidly administered intravenously; it has appropriate coverage against potential pathogens; it has a long half-life, so a second dose may not be required during most procedures; and it has a safety profile similar to that of other commonly used antibiotics. The purpose of this prospective, randomized, double-blind study was to assess the efficacy and safety of antibiotic prophylaxis with ertapenem compared to cefotetan in patients undergoing elective colorectal procedures. (2)

At 51 centers in the United States between May 2002 and March 2005, all patients 18 years of age or older who were scheduled to undergo elective open surgery of the colon or rectum and had sufficient time for bowel preparation were eligible for inclusion in the study. Patients were excluded if they

* needed emergency colorectal surgery,

* needed a second planned surgery requiring antibiotic prophylaxis,

* were having an elective colorectal procedure for revision of a previous surgery,

* underwent laparoscopic-assisted surgery, or

* needed an isolated rectal procedure.

Also excluded were patients

* who had bacterial infections at the time of surgery or required antimicrobial therapy up to one week before surgery;

* for whom the study medication was contraindicated;

* with active inflammatory bowel disease, neutropenia, or immunosuppression;

* with abnormal amino-transferase levels or prothrombin times that were at least three times that of the upper limit of the normal range; and

* who were pregnant or nursing.

Patients were assigned to receive either a single dose of 1 g of ertapenem or 2 g of cefotetan to be infused over a 30-minute period within 60 minutes before the initial surgical incision. Patients who completed a standard bowel preparation before surgery and who received a full dose of the study medication were included in a modified intention-to-treat analysis. Patients were included in a per-protocol analysis if they met the modified intention-to-treat criteria and, in addition, they

* received the study medication within two hours before the surgical incision and six hours before surgical closure,

* underwent a four-week follow-up assessment,

* did not receive any non-study antibiotics in the week before surgery, and

* did not have a distant-site infection.

The primary endpoints were the proportion of patients who could be evaluated and for whom prophylaxis was successful at the four-week follow-up assessment after surgery, as well as any other clinical adverse events, including medication-related adverse events. Success was defined as no signs or symptoms of infection at the surgical site and no further need for antimicrobial therapy or surgery.

All patients gave a complete medical history, underwent a physical examination, and gave information to be used as a baseline regarding preoperative risk factors for postoperative infections. Vital signs were measured daily while the patient was hospitalized and at the four-week follow-up assessment. Wound assessments were performed at least every other day for up to seven days during hospitalization as well as at discharge and at the four-week follow-up visit. Patients were monitored for clinical adverse events daily during hospitalization and by telephone after discharge until 14 days after the administration of the study medications. Common statistical procedures, including multiple logistic regression techniques, were used to analyze the data, and a modified intention-to-treat analysis also was performed.

Findings. Of the 1,002 patients who were randomly assigned to the study groups, 901 qualified for the modified intention-to-treat analysis and 672 were included in the per-protocol analysis. In the modified intention-to-treat analysis, the overall failure rates were 40.2% in the ertapenem group and 50.9% in the cefotetan group (absolute difference -10.7%, 95% confidence interval [CI] -17.1 to -4.2). Additionally, the most common reason for failure of prophylaxis in both groups was surgical site infection, with an infection rate of 17.1% in the ertapenem group and 26.2% in the cefotetan group (absolute difference -9.1, 95% CI-14.4 to -3.7). In the per-protocol analysis, the overall failure rates were 28% in the ertapenem group and 42.8% in the cefotetan group (absolute difference -14.8%, 95% CI-21.9 to -7.5). Both of these analyses fulfilled statistical criteria for the superiority of ertapenem.